Nature Communications Publication: PhD research of UMBI Young Research Fellow Dr. Saiful Effendi

Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, is
characterised by biallelic inactivation of von Hippel Lindau tumour suppressor gene (VHL),
mTORC1 signalling pathway activation and accumulation of cytoplasmic lipid. Inhibitors
against receptor tyrosine kinases (e.g. VEGFR and PDGFR) and the mTORC1 complex are
the current clinically approved therapies for ccRCC. Nevertheless, the overall objective
response rates especially for advanced ccRCC remain low, with 5-year survival at less than
10%.
A recent study by our young research fellow, Saiful Effendi Bin Syafruddin who just
completed his PhD at the University of Cambridge, published this month in Nature
Communications, elucidates previously uncharacterised molecular mechanisms underlying
ccRCC pathogenesis. The new results show that a cellular signalling network centred around
Kruppel-like factor 6 (KLF6), a super enhancer-associated zinc finger transcription factor,
promotes ccRCC growth by supporting lipid metabolism and mTORC1 activity. KLF6
activates mTORC1 through the expression of the secreted factor PDGFB, a ligand for the
PDGFR receptor. Thus, these results reveal a molecular link between two approved kidney
cancer therapeutic targets, PDGFR and mTORC1. The new results also highlight the links
between super enhancer-driven transcriptional networks and the activity of essential
metabolic pathways. Detailed understanding of such links could pave the way for novel
therapeutic intervention strategies.

The study entitled A KLF6-driven transcriptional network links lipid homeostasis and
tumour growth in renal carcinoma by Syafruddin et al. has been published in Nature
Communications on 11 March 2019.

https://www.nature.com/articles/s41467-019-09116-x